Brain grafting and pallidotomy are being used to treat patients suffering from Parkinson's disease who are refractory to medical therapy. Behavioral recovery following caudate cavitation in Parkinsonian monkeys focused our attention on potentially beneficial host responses to grafting. Following injury, the CNS produces neurotrophic factors which promote neurite outgrowth and glial proliferation. We have explored the therapeutic potential of growth factors to preventing or revere biochemical and behavioral deficits in rodent and primate models of Parkinson's disease. To deliver growth factors to gray matter we are developing methods for convection-enhanced direct infusion into the striatum. We used convection to enhance the distribution of large molecules injected into the striatum in rats, measured using immunohistochemistry and quantitative autoradiography. We are now exploring the continuously delivery of proteins such as BDNF, to the striatum of MPTP-lesioned monkeys. Recent electrophysiologic and anatomic studies have shown hyperactivity of neurons in the subthalamic and globus palladium interna nuclei produce the symptoms of Parkinson's disease. Accordingly, we are exploring the use of excitatory amino acids to destroy the neurons of the globus pallidus interna in monkeys as a novel therapy.